Department of Pathology, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou, 515031, People's Republic of China.
Department of Breast Center, Cancer Hospital of Shantou University Medical College, No.7 Raoping Road, shantou, 515031, People's Republic of China.
Breast Cancer Res Treat. 2020 Jul;182(1):21-33. doi: 10.1007/s10549-020-05673-8. Epub 2020 May 15.
Previous studies have indicated that transient receptor potential (TRP) channels can influence cancer development. The TRPC subfamily consists of seven subtypes, TRPC1 - TRPC7. Interestingly, the expression levels of TRPC1 have been shown to be totally different in different breast cancer cell lines. Nevertheless, the underlying mechanism remains unknown. In this study, we explore the significance of TRPC1 expression in breast cancer.
Immunohistochemical TRPC1 staining was performed in 278 samples. TRPC1 expression in different breast tissues were examined. Then, the influence of TRPC1 on migration, invasion and proliferation was explored. We analyzed the protein of TRPC1 by Western blot to prove which pathway may be involved in. Finally, we use online database to predict the prognosis of TRPC1 in breast cancer.
Through immunohistochemistry and in vitro experiments, we found that the expression level of TRPC1 was higher in breast cancer cells as compared with that in normal breast epithelial cells. Moreover, the expression level of TRPC1 was different between estrogen receptor-positive (ER +) and -negative (ER -) breast cancer. It was shown that TRPC1 inhibited MCF7 cell proliferation, migration, and invasion in vitro. Western blotting revealed that TRPC1 inhibited the PI3K/AKT pathway and epithelium-mesenchymal transformation, leading to subsequent inhibition of cell proliferation and metastasis. In luminal A and luminal B patients, those with high TRPC1 expression had a better prognosis. On the contrary, in basal-like and triple-negative breast cancer (TNBC) subtypes, patients with high-TRPC1 expression had a worse prognosis.
We confirmed that TRPC1 was high expression in breast cancer. Overexpression of TRPC1 inhibits proliferation and migration of ER + breast cancer and gives a better prognosis by inhibiting PI3K/AKT pathway activation. TRPC1 may be an independent prognostic predictor in breast cancer patients.
先前的研究表明瞬时受体电位 (TRP) 通道可影响癌症的发展。TRPC 亚家族由七种亚型组成,TRPC1-TRPC7。有趣的是,不同乳腺癌细胞系中 TRPC1 的表达水平完全不同。然而,其潜在机制尚不清楚。在这项研究中,我们探讨了 TRPC1 表达在乳腺癌中的意义。
对 278 例样本进行免疫组织化学 TRPC1 染色。检测不同乳腺组织中 TRPC1 的表达情况。然后,探讨 TRPC1 对迁移、侵袭和增殖的影响。我们通过 Western blot 分析 TRPC1 蛋白,以证明可能涉及的途径。最后,我们使用在线数据库预测 TRPC1 在乳腺癌中的预后。
通过免疫组化和体外实验,我们发现乳腺癌细胞中 TRPC1 的表达水平高于正常乳腺上皮细胞。此外,TRPC1 的表达水平在雌激素受体阳性(ER+)和阴性(ER-)乳腺癌之间存在差异。结果表明,TRPC1 抑制 MCF7 细胞在体外的增殖、迁移和侵袭。Western blot 显示,TRPC1 抑制了 PI3K/AKT 通路和上皮间质转化,从而抑制了细胞增殖和转移。在管腔 A 和管腔 B 患者中,TRPC1 高表达者的预后较好。相反,在基底样和三阴性乳腺癌(TNBC)亚型中,TRPC1 高表达者的预后较差。
我们证实 TRPC1 在乳腺癌中高表达。TRPC1 的过表达通过抑制 PI3K/AKT 通路的激活,抑制 ER+乳腺癌的增殖和迁移,并提供更好的预后。TRPC1 可能是乳腺癌患者的独立预后预测因子。